Selective controlled manipulation of polymers

ABSTRACT

The present invention provides partial and complete shielding approaches to alter the cross-linking characteristics of irradiated polymers, such as polyethylene. Irradiated polymers and fabricated articles, such as medical prosteses, comprising irradiated polymers also are provided.

RELATED APPLICATION

This application is a 371 of PCT/US01/47507 filed on Dec. 11, 2001,which claims benefit to U.S. Provisional No. 60/254,560, filed on Dec.12, 2000, the entirety of which is hereby incorporated by reference.

BACKGROUND OF THE INVENTION

The present invention relates to the selective, controlled manipulationof polymers and polymer alloys using radiation chemistry, which makespossible the tailoring of polymer properties for a specific intendeduse. The present invention finds particular application in theorthopedic field, including the formation of medical prosthesis, such aship, knee, shoulder, and finger implants.

Methods of irradiating polymers are described in U.S. Pat. No.5,879,400. In general, this patent describes medical prosthesis formed,at least in part, of a melt-irradiated high molecular weightpolyethylene. The disclosed melt-irradiation process improves the wearresistance of the polymer, thus addressing the problem of severe adverseeffects associated with the use of less wear resistant polymers. U.S.Pat. No. 5,879,400 describes, among other things, heating the polymersto or above the melting point, irradiating the polymer, and cooling thepolymer.

International Application No. PCT/US97/02220 (WO 97/29793) alsodescribes the irradiation of polymers that are useful in the orthopedicfield. In this application, several methods of increasing the wearcharacteristics of polymers are described. The application describes,among other things, an irradiation procedure wherein the polymer isirradiated at room temperature or below. Following irradiation, thepolymer can be heated to or above the melting temperature to remove anyresidual free radicals through the process of recombination. Theapplication also describes another irradiation method in which thepolymer is pre-heated to a temperature above room temperature, but belowthe melting temperature, and irradiated. Following irradiation, thepolymer may be subsequently melted by heating it to the meltingtemperature or above to substantially eliminate any detectable freeradicals via the process of recombination.

WO 97/29793 also describes methods of irradiating polymers in which theheat generated by the irradiation is sufficient to at least partiallymelt the polymer, and is described as “adiabatic melting”. “Adiabaticmelting” refers to heating induced by radiation, which leads to anincrease of the temperature of the polymer with substantially littleloss of heat to the surroundings. The application describes an adiabaticmelting method in which the polymer is preheated to a temperature belowthe melting point, then irradiated with enough total dose and at a highenough dose rate to at least partially melt the polymer crystals.Subsequent to this warm-irradiation, the polymer also can be heated toor above the melting temperature such that any residual free radicalsare eliminated. The application also describes another irradiation,adiabatic melting method that is similar to the method described above,except that the polymer is provided at room temperature or below.

International Application No. PCT/US99/16070, describes the use ofirradiated polymers for hip joints with an extended range of motion. Inparticular, this application relates to the use of wear resistantirradiated polymers in hip joint prostheses. The wear resistance of thepolymers allows for the use of combinations of cup thicknesses and headdiameters that result in an extended range of motion as compared withconventional replacement hip joints, the wear resistance of which wasunable to support cup thickness and head diameter combinations thatallowed for extended ranges of motion.

Other approaches of irradiation are disclosed in U.S. Pat. Nos.6,281,264; 6,245,276; 6,242,507; 6,228,900; 6,184,265; 6,165,220; and6,017,975.

Despite the major improvements in the wear resistance of orthopedicprostheses and the design of hip prostheses allowing an improved rangeof motion, there remains a significant need for further improvements.For example, the irradiation of polymers is known to change themechanical properties of the polymer. Following irradiation andsubsequent melting and annealing, polyethylene polymers exhibit reducedtoughness, reduced modulus of elasticity, reduced shear strength andreduced ultimate tensile strength. In the case of hip prostheses, forexample, larger head diameters often require the use of thinner liners.The locking mechanisms on these liners (used to lock the liner to metalshells) may fail due to the undesirable changes in the mechanicalproperties of the polymers following irradiation. The situation issimilar in knee prostheses. In knee prostheses, intricate lockingmechanism, usually in the form of snap-lock, pegs and pins, are used tostabilize the liners on a metal tray. These locking mechanisms rely onthe high shear strength of the polymer used. When irradiated, theadverse effects on the shear strength of the polymer may jeopardize thestability of the liner. Similar problems arise in other types of medicalprostheses.

These and other aspects of the invention will become apparent to theskilled artisan in view of the teachings contained herein.

SUMMARY OF THE INVENTION

It is an object of the present invention to provide improved polymersfor various uses, including medical uses such as prosthetics. Inaccomplishing this object and other objects, there are provided, inaccordance with one aspect of the invention, an irradiated compositioncomprising a polymer, wherein the composition having a gradient ofcross-linking perpendicular to the direction of irradiation. The polymercan be selected from the group consisting of high density polyethylene,low density polyethylene, linear low density polyethylene, ultra lowdensity polyethylene, very low density polyethylene, ultra highmolecular weight polyethylene, and high molecular weight polyethylenes.

In accordance with another aspect of the invention, there are providedmethods of making a cross-linked composition comprising an irradiatedpolymer, said cross-linked composition having a gradient ofcross-linking perpendicular to the direction of irradiation, wherein themethod comprises:

(A) shielding part or all of composition comprising a polymer; and

(B) irradiating said partially shielded composition of (A) to yield thecross-linked polymer. The shield can be made of, among other things, amaterial selected from the group consisting of ceramics, metals, glassand polymers. The polymer can be selected from the group consisting ofhigh density polyethylene, low density polyethylene, linear low densitypolyethylene, ultra low density polyethylene, very low densitypolyethylene, ultra high molecular weight polyethylene, and highmolecular weight polyethylene. According to one aspect of the invention,the irradiation step comprises one or more, in any order, of theprocedures selected from the group consisting of procedures (a)–(g):

(a) (i) heating the polymer to at or above the melting temperature ofthe polymer, and

-   -   (ii) irradiating the polymer in the molten state;

(b) (i) providing the polymer at or below room temperature, and

(ii) irradiating the polymer;

(c) (i) providing the polymer at or below room temperature, and

(ii) irradiating the polymer with a high enough total dose and/or at afast enough dose rate to generate enough heat in the polymer to resultin at least a partial melting of the crystals of the polymer;

(d) (i) providing the polymer at or below room temperature,

(ii) irradiating the polymer, and

(iii) heating the irradiated polymer to at or above the meltingtemperature of the polymer;

(e) (i) heating the polymer to a temperature above room temperature andbelow the melting temperature, and

(ii) irradiating the heated polymer;

(f) (i) heating the polymer to a temperature above room temperature andbelow the melting temperature,

-   -   (ii) irradiating the heated polymer, and    -   (iii) heating the irradiated polymer to at or above the melting        temperature of the polymer; and/or

(g) (i) heating the polymer to a temperature above room temperature andbelow the melting temperature, and

(ii) irradiating the heated polymer with a high enough total dose and/orat a fast enough dose rate to generate enough heat in the polymer toresult in at least a partial melting of the crystals of the polymer.

In accordance with another aspect of the invention, there are providedmedical prostheses comprising an irradiated polymer, said prosthesishaving a gradient of cross-linking perpendicular to the direction ofirradiation. The polymer can be selected from the group consisting ofhigh density polyethylene, low density polyethylene, linear low densitypolyethylene, ultra low density polyethylene, very low densitypolyethylene, ultra high molecular weight polyethylene, and highmolecular weight polyethylene.

In accordance with still another aspect of the invention, there areprovided methods of making medical prostheses comprising an irradiatedpolymer, said medical prosthesis having a gradient of cross-linkingperpendicular to the direction of irradiation, said method comprising:

(A) shielding part or all of a composition comprising said polymer; and

(B) irradiating said partially shielded composition. The shield can bemade of, among other things, a material selected from the groupconsisting of ceramics, metals, glasses and polymers. The polymer can beselected from the group consisting of high density polyethylene, lowdensity polyethylene, linear low density polyethylene, ultra low densitypolyethylene, very low density polyethylene, ultra high molecular weightpolyethylene, and high molecular weight polyethylene. According to oneaspect of the invention, the irradiation step comprises one or more, inany order, of the procedures selected from the group consisting ofprocedures (a)–(g):

(a) (i) heating the polymer to at or above the melting temperature ofthe polymer, and

-   -   (ii) irradiating the polymer in the molten state;

(b) (i) providing the polymer at or below room temperature, and

-   -   (ii) irradiating the polymer;

(c) (i) providing the polymer at or below room temperature, and

-   -   (ii) irradiating the polymer with a high enough total dose        and/or at a fast enough dose rate to generate enough heat in the        polymer to result in at least a partial melting of the crystals        of the polymer;

(d) (i) providing the polymer at or below room temperature,

-   -   (ii) irradiating the polymer, and    -   (iii) heating the irradiated polymer to at or above the melting        temperature of the polymer;

(e) (i) heating the polymer to a temperature above room temperature andbelow the melting temperature, and

-   -   (ii) irradiating the heated polymer;

(f) (i) heating the polymer to a temperature above room temperature andbelow the melting temperature,

-   -   (ii) irradiating the heated polymer, and    -   (iii) heating the irradiated polymer to at or above the melting        temperature of the polymer; and/or

(g) (i) heating the polymer to a temperature above room temperature andbelow the melting temperature, and

-   -   (ii) irradiating the heated polymer with a high enough total        dose and/or at a fast enough dose rate to generate enough heat        in the polymer to result in at least a partial melting of the        crystals of the polymer.

The invention is further disclosed and exemplified by reference to thetext and drawings that follow.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a graph plotting the trans vinylene index versus the depthinto the core of an irradiated ultra-high molecular weight polyethylene(“UHMWPE”) disc.

FIG. 2 depicts a postulated molecular morphology evolution in twodifferent irradiation processes, namely CISM and WIAM (defined anddescribed in greater detail below). FIG. 2 shows that the crosslinkdistribution in the CISM process is more statistical (random) in theamorphous phase as compared with the WIAM process, in which the finalcrosslink distribution is highly non-uniform with a biphasic structure.X represents the crystallinity and T represents temperature. Here, the“% dose” indicates the percent of the total radiation dose intended tobe delivered to the polymer during the irradiation step.

FIG. 3 depicts a schematic of a complete coverage shield covering aUHMWPE construct.

FIG. 4 depicts the construct of FIG. 3 that has been bisected formicrotoming.

FIG. 5 shows the variation of the trans vinylene index as a function ofdistance for UHMWPE irradiated at room temperature.

FIG. 6 shows the variation of the trans vinylene index as a function ofdistance for UHMWPE irradiated at 125° C.

FIG. 7 shows the variation of the trans vinylene index as a function ofdistance for UHMWPE irradiated at 2 different temperature (25° C. and125° C.) and different complete (that is, full) coverage shieldthicknesses (1 mm, 9 mm, and 15 mm).

FIG. 8 depicts a UHMWPE construct covered with a 1 cm thick aluminumpartial shield (hole in center).

FIG. 9 depicts the construct of FIG. 8 that has been bisected formicrotoming.

FIG. 10 shows the variation of the trans vinylene index as a function ofdistance for irradiated UHMWPE.

FIG. 11 compares unradiated UHMWPE (panel a) to the partially-shieldUHMWPE (panel b) according to FIG. 8.

FIG. 12 depicts various exemplary shield geometry's, which can be usedaccording to the invention, such as in an arrangement according to FIG.21.

FIG. 13 depicts the use of the present invention in the fabrication ofan acetabular liner of a hip prosthesis.

FIG. 14 depicts the use of the present invention in the fabrication of amobile bearing knee prosthesis (such as a rotating platform knee).

FIG. 15 depicts the use of the present invention in the fabrication of aknee meniscus prosthesis.

FIG. 16 depicts the use of the present invention in the fabrication of ashoulder meniscus prosthesis.

FIG. 17 depicts the use of the present invention in the fabrication of aspacer for a finger joint.

FIG. 18 depicts exemplary shield edge geometry's and the resultantirradiation penetration envelopes. One set of illustrations showsshields that fully block the radiation from the covered area, while theother set of illustrations shows shields that partially block theradiation from the covered area.

FIG. 19 is an illustration of the effect of a radiation shield on thedepth of penetration of electron radiation at 10 MeV.

FIG. 20 is a depiction of the “teardrop” electron penetration envelopesignature left by electron radiation as it travels through a polymer.

FIG. 21 illustrates the irradiation of a polymer preform using both aring-shaped and disc-shaped shield in sequence.

FIG. 22 illustrates an embodiment of partial coverage shielding asdescribed herein.

FIG. 23 illustrates an embodiment of complete coverage shielding asdescribed herein.

FIG. 24 illustrates another embodiment of complete coverage shielding asdescribed herein.

FIG. 25 illustrates (a) the irradiation of the thin sections sandwichedwith dosimeters along with (b) the 96 mm thick sample. The former wasused in determining the e-beam cascade using the TVI method, while thelatter was used to determine the cascade by evaluating the absorbed doselevels in the sandwiched dosimeters.

FIG. 26 shows the normalized TVI variation as a function of depth awayfrom e-beam incidence surface as compared with the normalized dose levelmeasured through the Far West dosimeters. The agreement between the twocurves supports that the TVI yield is directly proportional to theabsorbed dose level

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to the selective, controlled irradiationmanipulation of polymers, including (1) compositions that are homogenousin terms of a given type of polymer content (for example, homopolymers),and (2) polymer alloys. The manipulation of the polymers, as describedherein, allows the tailoring of the physical properties of the polymersto achieve a desired result. The polymers may be used in a variety ofapplications, including in the manufacture of medical prostheses.

By “ultra-high molecular weight polyethylene” or “UHMWPE” is meantchains of ethylene that have molecular weights in excess of about500,000 g/mol, preferably above about 1,000,000 g/mol, and morepreferably above about 2,000,000 g/mol. Often the molecular weights canbe at least as high as about 8,000,000 g/mol. By initial averagemolecular weight is meant the average molecular weight of the UHMWPEstarting material, prior to any irradiation.

By “low-density polyethylene” or LDPE is meant a polyethylene with adensity range of about 0.910–0.932 g/cm³. The LDPE is usuallypolymerized from ethylene gas in presence of a few mol percent of aco-monomer (1-pentene, 1-hexene, etc.) with shorter branches.

By “high-density polyethylene” or HDPE is meant a polyethylene with adensity in excess of about 0.936 g/cm³. The HDPE is usually polymerizedfrom ethylene gas in presence of a few mol percent of a co-monomer(1-pentene, 1-hexene, etc.) to achieve substantially unbranchedpolyethylene chains.

By “linear-low-density polyethylene” or LLDPE is meant a polyethylenewith a density range of about 0.910–0.942 g/cm³. The LLDPE ispolymerized from ethylene gas with the addition of short branches(shorter than LDPE) to keep the density lower than what is observed inHDPE. LLDPEs are copolymers of ethylene and alpha-olefins polymerizedwith either Ziegler-Natta or metallocene catalysts. The molecularstructure exhibits short-chain branching. Generally, the metallocenechemistry yields a more uniform distribution of the short-chain branchesthan Ziegler-Natta catalysts.

The term “embodiment” is non-limiting and includes examples and aspectsof the invention, which are combinable in view of the teachingscontained herein.

The term “about” in the context of numerical values and ranges refers tovalues or ranges that approximate or are close to the recited values orranges such that the invention can perform as intended, such as having adesired degree of cross-linking and/or a desired lack of free radicals,as is apparent from the teachings contained herein. This termencompasses values beyond those resulting from systematic error.

Examples of commercially-available UHMWPE resins (in powder form)include Hifax Grade 1900 polyethylene (obtained from Montell,Wilmington, Del.), having a molecular weight of about 2 million g/moland not containing any calcium stearate; GUR 1050 (obtained from HoechstCelanese Corp., Germany), having a molecular weight of about 4–5 milliong/mol and not containing any calcium stearate; GUR 1150 (obtained fromHoechst Celanese Corp., Germany), having a molecular weight of about 4–5million g/mol and containing 500 ppm of calcium stearate; GUR 1020(obtained from Hoechst Celanese Corp., Germany), having a molecularweight of about 2 million g/mol and not containing any calcium stearate;and GUR 1120 (obtained from Hoechst Celanese Corp., Germany), having amolecular weight of about 2 million g/mol and containing 500 ppm ofcalcium stearate. Preferred UHMWPEs for medical applications are GUR1050 and GUR 1020. By resin is meant powder.

UHMWPE powder can be consolidated using a variety of differenttechniques, e.g., ram extrusion, compression molding, or directcompression molding. In ram extrusion, the UHMWPE powder is pressurizedthrough a heated barrel whereby it is consolidated into a rod stock,i.e., bar stock (can be obtained, e.g., from Westlake Plastics, Lenni,Pa.). In compression molding, the UHMWPE powder is consolidated underhigh pressure into a mold (can be obtained, e.g., from Poly-Hi Solidur,Fort Wayne, Ind., or Perplas, Stanmore, U.K.). The shape of the mold canbe, e.g., a thick sheet. Direct compression molding is preferably usedto manufacture net shaped products, e.g., acetabular components ortibial knee inserts (can be obtained, e.g., from Zimmer, Inc., Warsaw,Ind.). In this technique, the UHMWPE powder is compressed directly intothe final shape.

Some of the commercial sources of LDPE along with approximate densityranges are as follows: Novapol (0.917–0.924 g/cm³) from Nova Chemical,Petrothene (0.9175–0.932 g/cm³) from Equistar, and Escorene (0.913–0.929g/cm³) from Exxon Mobile. The LDPE generally exhibits density ranges ofabout 0.910 and 0.932 g/cm³.

Some of the commercial sources of HDPE along with approximate densityranges area as follows: Sclair (0.936–0.962 g/cm³) and Novapol(0.945–0.956 g/cm³) from Nova Chemical, Alathon (0.949–0.965 g/cm³) andPetrothene (0.940–0.961 g/cm³) from Equistar, and Escorene (0.941–0.966g/cm³) from Exxon Mobile. The HDPE generally exhibits a density oflarger than about 0.936 g/cm³.

Some of the commercial sources of LLDPE along with approximate densityranges are as follows: Dowlex (0.917–0.941 g/cm³) from Dow Chemical,Novapol (0.917–0.926 g/cm³) and Sclair (0.918–0.930 g/cm³) from NovaChemical, Petrothene (0.918–0.9305 g/cm³) from Equistar, and Escorene(0.917–0.938 g/cm³) from Exxon Mobile. The LLDPE generally exhibitsdensity ranges of about 0.910 and 0.942 g/cm³.

Some of the commercial sources of VLDPE or ULDPE along with approximatedensities are as follows: Attane (ranging from about 0.904–0.913 g/cm³)from Dow Chemical, Sclair (0.911 g/cm³) from Nova Chemical. These VLDPEand ULDPE generally exhibit a density of less than about 0.913 g/cm³.

Use of the phrases such as “radiation treated,” “irradiated,” or thelike, mean that the polymer or polymer alloy have been treated withradiation, including gamma radiation or electron radiation, so as toinduce cross-links between the polymeric chains of the polymer.

“Substantially no detectable free radicals” means that substantially nofree radicals are present to deleteriously affect the desired propertiesof the irradiated material and can be measured as described in Jahan etal., J. Biomedical Materials Research 25:1005 (1991). Free radicalsinclude, for example, allyl and/or alkyl type or peroxy type freeradicals. A polymer that has been irradiated below its melting pointwith ionizing radiation contains cross-links as well as long-livedtrapped free radicals. These free radicals react with oxygen over thelong-term and result in the embrittlement of the polymer throughoxidative degradation. The free radicals can be eliminated by anymethod, which gives this result, including, for example, heating thepolymer to above its melting point to permit the free radicals torecombine.

References herein to the melting point of a polymer refer to the peakmelting temperature measured in DSC.

1. Polymer Materials

The selective, controlled manipulation of polymers using irradiationchemistry can be achieved, in one aspect, by the selection of thepolymer to be irradiated. The properties of the polymer, such asdensity, molecular weight, crystallinity, and/or crosslink densitycontribute to the properties of the irradiated polymer and can beselected and combined to yield an irradiated polymer with a desired setof properties.

a. Polymers

Any suitable polymer may be used in accordance with the presentinvention. Suitable polymers include those that are biocompatible andbiostable. Exemplary polymers include types of polyethylenes.

Polyethylene polymers are particularly suitable for use with the presentinvention. Suitable polyethylenes include, but are not limited to, ultrahigh molecular weight polyethylene (UHMWPE), high-density polyethylene(HDPE), low density polyethylene (LDPE), linear low density polyethylene(LDPE), each of which have been defined above. Additionally, theinvention can be used with ultra low density polyethylene (ULDPE), verylow density polyethylene (VLDPE), The VLDPE and ULDPE are defined as apolyethylene with a density less than about 0.913 g/cm³. Such polymersare known to those of skill in the art and available from commercialsource. For instance ULDPE and VLDPE are available from Dow Chemicalunder the tradename of Attane and from Nova Chemical under the tradenameof Sclair.

It also is suitable to use polymer alloys in accordance with the presentinvention. As used herein, a polymer alloy is a blend of two or morepolymers with the identical repeat unit with differences in theirmolecular structures. The differences could be in the molecular weightsand/or degrees of branching of the polymers in some instances leading todifferences in their physical properties such as density. Suitablealloys include polyethylene/polyethylene alloys in which theconstituents of the alloy have different molecular weights, differentdensities, and/or different degrees of branching. For instance, an alloymade out of at least two or more of the following polyethylenes: LDPE,HDPE, LLDPE, ULDPE, VLDPE and other polyethylenes. In a polymer alloythe constituent polymers could be either miscible or immiscible. Thepolymer alloys are known to co-crystallize during crystallization. Insome alloys the crystallization of the constitutive polymers occurseparately to form their respective crystalline structures.

2. Methods and Sequence of Irradiation

The selective, controlled manipulation of polymers and polymer alloysusing radiation chemistry can, in another aspect, be achieved by theselection of the method by which the polymer is irradiated. Theparticular method of irradiation employed, either alone or incombination with other aspects of the invention, such as the polymer orpolymer alloy chosen, contribute to the overall properties of theirradiated polymer.

Gamma irradiation or electron radiation may be used. In general, gammairradiation results in a higher radiation penetration depth thanelectron irradiation. Gamma irradiation, however, generally provides lowradiation dose rate and requires a longer duration of time, which canresult in more in-depth and extensive oxidation, particularly if thegamma irradiation is carried out in air. Oxidation can be reduced orprevented by carrying out the gamma irradiation in an inert gas, such asnitrogen, argon, or helium, or under vacuum. Electron irradiation, ingeneral, results in a more limited dose penetration depth, but requiresless time and, therefore, reduces the risk of extensive oxidation if theirradiation is carried out in air. In addition if the desired doselevels are high, for instance 20 Mrad, the irradiation with gamma maytake place over one day, leading to impractical production times. On theother hand, the dose rate of the electron beam can be adjusted byvarying the irradiation parameters, such as conveyor speed, scan width,and/or beam power. With the appropriate parameters, a 20 Mradmelt-irradiation can be completed in for instance less than 10 minutes.The penetration of the electron beam depends on the beam energy measuredby million electron-volts (MeV). Most polymers exhibit a density ofabout 1 g/cm³, which leads to the penetration of about 1 cm with a beamenergy of 2–3 MeV and about 4 cm with a beam energy of 10 MeV. Ifelectron irradiation is preferred, the desired depth of penetration canbe adjusted based on the beam energy. Accordingly, gamma irradiation orelectron irradiation may be used based upon the depth of penetrationpreferred, time limitations and tolerable oxidation levels.

a. Irradiation Methods

(i) Irradiation in the Molten State (IMS)

Melt-irradiation, or irradiation in the molten state (“IMS”), isdescribed in detail in U.S. Pat. No. 5,879,400. In the IMS process, thepolymer to be irradiated is heated to at or above its melting point.Then, the polymer is irradiated. Following irradiation, the polymer iscooled.

Prior to irradiation, the polymer is heated to at or above its meltingtemperature and maintained at this temperature for a time sufficient toallow the polymer chains to achieve an entangled state. A sufficienttime period may range, for example, from about 5 minutes to about 3hours. For UHMWPE, the polymer may be heated to a temperature betweenabout 145° C. and about 230° C., preferably about 150° C. to about 200°C.

Gamma irradiation or electron radiation may be used. In general, gammairradiation results in a higher radiation penetration depth thanelectron irradiation. Gamma irradiation, however, generally provides lowradiation dose rate and requires a longer duration of time, which canresult in more in-depth oxidation, particularly if the gamma irradiationis carried out in air. Oxidation can be reduced or prevented by carryingout the gamma irradiation in an inert gas, such as nitrogen, argon, orhelium, or under vacuum. Electron irradiation, in general, results in amore limited dose penetration depth, but requires less time and,therefore, reduces the risk of extensive oxidation if the irradiation iscarried out in air. In addition if the desired dose levels are high, forinstance 20 Mrad, the irradiation with gamma may take place over oneday, leading to impractical production times. On the other hand, thedose rate of the electron beam can be adjusted by varying theirradiation parameters, such as conveyor speed, scan width, and/or beampower. With the appropriate parameters, a 20 Mrad melt-irradiation canbe completed in for instance less than 10 minutes. The penetration ofthe electron beam depends on the beam energy measured by millionelectron-volts (MeV). Most polymers exhibit a density of about 1 g/cm³,which leads to the penetration of about 1 cm with a beam energy of 2–3MeV and about 4 cm with a beam energy of 10 MeV. The penetration ofe-beam is known to increase slightly with increased irradiationtemperatures. If electron irradiation is preferred, the desired depth ofpenetration can be adjusted based on the beam energy. Accordingly, gammairradiation or electron irradiation may be used based upon the depth ofpenetration preferred, time limitations and tolerable oxidation levels.

The temperature of melt-irradiation for a given polymer depends on theDSC (measured at a heating rate of 10° C./min during the first heatingcycle) peak melting temperature (“PMT”) for that polymer. In general,the irradiation temperature in the IMS process is about 2° C. higherthan the PMT, more preferably between about 2° C. and about 20° C.higher than the PMT, and most preferably between about 5° C. and about10° C. higher than the PMT.

The total dose of irradiation also may be selected as a parameter incontrolling the properties of the irradiated polymer. In particular, thedose of irradiation can be varied to control the degree of cross-linkingand crystallinity in the irradiated polymer. The total dose may rangefrom about 0.1 Mrad to as high as the irradiation level where thechanges in the polymer characteristics induced by the irradiation reacha saturation point. For instance the high end of the dose range could be20 Mrad for the melt-irradiation of UHMWPE, above which dose level thecrosslink density and crystallinity are not appreciably affected withany additional dose. The preferred dose level depends on the desiredproperties that will be achieved following irradiation. Additionally,the level of crystallinity in polyethylene is a strong function ofradiation dose level. See Dijkstra et al., Polymer 30: 866–73 (1989).For instance with IMS irradiation, a dose level of about 20 Mrad woulddecrease the crystallinity level of UHMWPE from about 55% to about 30%.This decrease in crystallinity may be desirable in that it also leads toa decrease in the elastic modulus of the polymer and consequently adecrease in the contact stress when a medical prosthesis made out of theIMS-treated UHMWPE gets in contact with another surface during in vivouse. Lower contact stresses are preferred to avoid failure of thepolymer through, for instance, subsurface cracking, delamination,fatigue, etc. The increase in the crosslink density is also desirable inthat it leads to an increase in the wear resistance of the polymer,which in turn reduces the wear of the medical prostheses made out of thecrosslinked polymer and substantially reduces the amount of wear debrisformed in vivo during articulation against a counterface. In general,the melt-irradiation and subsequent cooling will lead to a decrease inthe crystallinity of the irradiated polymer.

Exemplary ranges of acceptable total dosages are disclosed in greaterdetail in U.S. Pat. No. 5,879,400 and International Application WO97/29793. For example, preferably a total dose of about or greater than1 MRad is used. More preferably, a total dose of greater than about 20Mrad is used.

In electron beam IMS, the energy deposited by the electrons is convertedto heat. This primarily depends on how well the sample is thermallyinsulated during the irradiation. With good thermal insulation, most ofthe heat generated is not lost to the surroundings and leads to theadiabatic heating of the polymer to a higher temperature than theirradiation temperature. The adiabatic heating could also be induced byusing a high enough dose rate to minimize the heat loss to thesurroundings. In some circumstance, adiabatic heating may be detrimentalto the sample that is being irradiated. Gaseous by-products, such ashydrogen gas when PE is irradiated, are formed during the irradiation.During irradiation, if the adiabatic heating is rapid and high enough tocause rapid expansion of the gaseous by-products, and thereby notallowing them to diffuse out of the polymer, the polymer may cavitate.The cavitation is not desirable in that it leads to the formation ofdefects (such as air pockets, cracks) in the structure that could inturn adversely affect the mechanical properties of the polymer and invivo performance of the device made thereof.

The adiabatic temperature rise depends on the dose level, level ofinsulation, and/or dose rate. The dose level used in the irradiationstage is determined based on the desired properties. In general, thethermal insulation is used to avoid cooling of the polymer andmaintaining the temperature of the polymer at the desired irradiationtemperature. Therefore, the adiabatic temperature rise can be controlledby determining an upper dose rate for the irradiation. For instance forthe IMS of UHMWPE the dose rate should be less than about 5 Mrad/pass(only applicable for the e-beam and not gamma as gamma is inherently alow dose rate process). These considerations for optimization for agiven polymer of a given size are readily determined by the person ofskill in view of the teachings contained herein.

In embodiments of the present invention in which electron radiation isutilized, the energy of the electrons can be varied to alter the depthof penetration of the electrons, thereby controlling the degree ofcrosslinking and crystallinity following irradiation. The range ofsuitable electron energies is disclosed in greater detail inInternational Application WO 97/29793. In one embodiment, the energy isabout 0.5 MeV to about 12 MeV. In another embodiment the energy is about1 MeV to 10 MeV. In another embodiment, the energy is about 10 MeV.

(ii) Cold Irradiation (CIR)

Cold irradiation is described in detail in WO 97/29793. In the coldirradiation process, a polymer is provided at room temperature or belowroom temperature. Preferably, the temperature of the polymer is about20° C. Then, the polymer is irradiated. In one embodiment of coldirradiation, the polymer may be irradiated at a high enough total doseand/or at a fast enough dose rate to generate enough heat in the polymerto result in at least a partial melting of the crystals of the polymer.

Gamma irradiation or electron radiation may be used. In general, gammairradiation results in a higher dose penetration depth than electronirradiation. Gamma irradiation, however, generally requires a longerduration of time, which can result in more in-depth oxidation,particularly if the gamma irradiation is carried out in air. Oxidationcan be reduced or prevented by carrying out the gamma irradiation in aninert gas, such as nitrogen, argon, or helium, or under vacuum. Electronirradiation, in general, results in a more limited dose penetrationdepths, but requires less time and, therefore, reduces the risk ofextensive oxidation. Accordingly, gamma irradiation or electronirradiation may be used based upon the depth of penetration preferred,time limitations and tolerable oxidation levels.

The total dose of irradiation may be selected as a parameter incontrolling the properties of the irradiated polymer. In particular, thedose of irradiation can be varied to control the degree of cross-linkingand crystallinity in the irradiated polymer. The preferred dose leveldepends on the molecular weight of the polymer and the desiredproperties that will be achieved following irradiation. For instance, toachieve maximum improvement in wear resistance using UHMWPE and the WIAM(warm irradiation and adiabatic melting) or CISM (cold irradiation andsubsequent melting) processes, a radiation dose of about 10 Mrad issuggested. To achieve maximum improvement in wear resistance using LDPEand LLDPE, a dose level greater than about 10 Mrad is suggested. Ingeneral, increasing the dose level with CIR would lead to an increase inwear resistance. If the CIR is carried out without post-irradiationmelt-annealing, the crystallinity and elastic modulus of the polymerwould increase. Following melt-annealing, however, these would decreaseto values lower than those prior to irradiation.

Exemplary ranges of acceptable total dosages are disclosed in greaterdetail in International Application WO 97/29793. In the embodimentsbelow, UHMWPE is used as the starting polymer. In one embodiment, thetotal dose is about 0.5 MRad to about 1,000 Mrad. In another embodiment,the total dose is about 1 MRad to about 100 MRad. In yet anotherembodiment, the total dose is about 4 MRad to about 30 MRad. In stillother embodiments, the total dose is about 20 Mares or about 15 Mares.

Other exemplary CIR dose levels for various polymers:

CIR Dose POLYMER Preferred More preferred Most preferred LDPE 0.5–1005–50 20 LLDPE 0.5–100 5–50 20 ULDPE 0.5–1000 5–300 and 10–200 100 VLDPE0.5–1000 5–300 and 10–200 150 HMWPE 0.5–100 5–50 20 UHMWPE 0.5–100 5–5015 HDPE 0.5–100 5–50 30

If electron radiation is utilized, the energy of the electrons also is aparameter that can be varied to tailor the properties of the irradiatedpolymer. In particular, differing electron energies will result indifferent depths of penetration of the electrons into the polymer. Thepractical electron energies range from about 0.1 MeV to 16 MeV givingapproximate iso-dose penetration levels of 0.5 mm to 8 cm, respectively.A preferred electron energy for maximum penetration is about 10 MeV,which is commercially available through vendors such as Studer (Daniken,Switzerland) or E-Beam Services (New Jersey, USA). The lower electronenergies may be preferred for embodiments where a surface layer of thepolymer is preferentially crosslinked with gradient in crosslink densityas a function of distance away from the surface.

(iii) Warm Irradiation (WIR)

Warm irradiation is described in detail in WO 97/29793. In the warmirradiation process, a polymer is provided at a temperature above roomtemperature and below the melting temperature of the polymer. Then, thepolymer is irradiated. In one embodiment of warm irradiation, which hasbeen termed “warm irradiation adiabatic melting” or “WIAM” the polymermay be irradiated at a high enough total dose and/or a high enough doserate to generate enough heat in the polymer to result in at least apartial melting of the crystals of the polymer.

The polymer may be provided at any temperature below its melting pointand above room temperature. The temperature selection depends on thespecific heat and the enthalpy of melting of the polymer and the totaldose level that will be used. The equation provided in InternationalApplication WO 97/29793 may be used to calculate the preferredtemperature range with the criterion that the final temperature ofpolymer immediately following the irradiation is not significantly abovethe melting point. Preheating of the polymer to the desired temperaturemay be done in an inert or non-inert environment.

Exemplary ranges of acceptable total dosages are disclosed in greaterdetail in International Application WO 97/29793. In one embodiment, theUHMWPE is preheated to about 20° C. to about 135° C. In one embodimentof WIAM, the UHMWPE is preheated to about 100° C. to just below themelting temperature of the polymer. In another embodiment of WIAM, theUHMWPE is preheated to a temperature of about 100° C. to about 135° C.In yet other embodiments of WIAM, the polymer is preheated to about 120°C. or about 130° C.

In general terms, the pre-irradiation heating temperature of the polymercan be adjusted based on the peak melting temperature (PMT) measure onthe DSC at a heating rate of 10° C./min during the first heat. In oneembodiment the polymer is heated to about 20° C. to about PMT. Inanother embodiment, the polymer is preheated to about 90° C. In anotherembodiment, the polymer is heated to about 100° C. In anotherembodiment, the polymer is preheated to about 30° C. below PMT and 2° C.below PMT. In another embodiment, the polymer is preheated to about 12°C. below PMT.

In the WIAM embodiment of WIR, the temperature of the polymer followingirradiation is at or above the melting temperature of the polymer.Exemplary ranges of acceptable temperatures following irradiation aredisclosed in greater detail in International Application WO 97/29793. Inone embodiment, the temperature following irradiation is about PMT toabout 200° C. In another embodiment, the temperature followingirradiation is about 145° C. to about 190° C. In yet another embodiment,the temperature following irradiation is about 146° C. to about 190° C.In still another embodiment, the temperature following irradiation isabout 150° C.

In WIR, gamma irradiation or electron radiation may be used. In general,gamma irradiation results in a higher dose penetration depth thanelectron irradiation. Gamma irradiation, however, generally requires alonger duration of time, which can result in more in-depth oxidation,particularly if the gamma irradiation is carried out in air. Oxidationcan be reduced or prevented by carrying out the gamma irradiation in aninert gas, such as nitrogen, argon, or helium, or under vacuum. Electronirradiation, in general, results in a more limited dose penetrationdepths, but requires less time and, therefore, reduces the risk ofextensive oxidation. Accordingly, gamma irradiation or electronirradiation may be used based upon the depth of penetration preferred,time limitations and tolerable oxidation levels. In the WIAM embodimentof WIR, electron radiation is used.

The total dose of irradiation may also be selected as a parameter incontrolling the properties of the irradiated polymer. In particular, thedose of irradiation can be varied to control the degree of cross-linkingand crystallinity in the irradiated polymer. Exemplary ranges ofacceptable total dosages are disclosed in greater detail inInternational Application WO 97/29793.

The dose rate of irradiation also may be varied to achieve a desiredresult. The dose rate is a prominent variable in the WIAM process. Inthe case of WIAM irradiation of UHMWPE, higher dose rates would providethe least amount of reduction in toughness and elongation at break. Thepreferred dose rate of irradiation would be to administer the totaldesired dose level in one pass under the electron-beam. One can alsodeliver the total dose level with multiple passes under the beam,delivering a (equal or unequal) portion of the total dose at each time.This would lead to a lower effective dose rate.

Ranges of acceptable dose rates are exemplified in greater detail inInternational Application WO 97/29793. In general, the dose rates willvary between 0.5 Mrad/pass and 15 Mrad/pass. The upper limit of the doserate depends on the resistance of the polymer to cavitation/crackinginduced by the irradiation.

If electron radiation is utilized, the energy of the electrons also is aparameter that can be varied to tailor the properties of the irradiatedpolymer. In particular, differing electron energies will result indifferent depths of penetration of the electrons into the polymer. Thepractical electron energies range from about 0.1 MeV to 16 MeV givingapproximate iso-dose penetration levels of 0.5 mm to 8 cm, respectively.The preferred electron energy for maximum penetration is about 10 MeV,which is commercially available through vendors such as Studer (Daniken,Switzerland) or E-Beam Services New Jersey, USA). The lower electronenergies may be preferred for embodiments where a surface layer of thepolymer is preferentially crosslinked with gradient in crosslink densityas a function of distance away from the surface.

(iv) Subsequent Melting (SM)—Substantial Elimination of DetectableResidual Free Radicals

Depending on the polymer or polymer alloy used, and whether the polymerwas irradiated below its melting point, there may be residual freeradicals left in the material following the irradiation process. Apolymer irradiated below its melting point with ionizing radiationcontains cross-links as well as long-lived trapped free radicals. Someof the free radicals generated during irradiation become trapped atcrystalline lamellae surfaces Kashiwabara, H. S. Shimada, and Y. Hori,Free Radicals and Crosslinking in Irradiated Polyethylene, Radiat. Phys.Chem., 1991, 37(1): p. 43–46; leading to oxidation-induced instabilitiesin the long-term. Jahan, M. S. and C. Wang, Combined Chemical andMechanical Effects on Free radicals in UHMWPE Joints DuringImplantation, Journal of Biomedical Materials Research, 1991, 25: p.1005–1017; Sutula, L. C., et al., Impact of gamma sterilization onclinical performance of polyethylene in the hip”, Clinical OrthopedicRelated Research, 1995, 3129: p. 1681–1689. The elimination of theseresidual, trapped free radicals through melt annealing is, therefore,desirable in precluding long-term oxidative instability of the polymer.Jahan M. S. and C. Wang, “Combined chemical and mechanical effects onfree radicals in UHMWPE joints during implantation”, Journal ofBiomedical Materials Research, 1991, 25: p. 1005–1017; Sutula, L. C., etal., “Impact of gamma sterilization on clinical performance ofpolyethylene in the hip”, Clinical Orthopedic Related Research, 1995,319: p. 28–4.

If there are residual free radicals remaining in the material, these maybe reduced to substantially undetectable levels, as measured by electronspin resonance or other tests, through annealing of the polymer abovethe melting point of the polymeric system used. The melt annealingallows the residual free radicals to recombine with each other. If for agiven system the preform does not have substantially any detectableresidual free radicals following irradiation, then a melt annealing stepmay be omitted. Also, if for a given system the concentration of theresidual free radicals are low enough to not lead to degradation ofdevice performance, the melt annealing step may be omitted. In some ofthe lower molecular weight and lower density polyethylenes, the residualfree radicals may recombine with each other even at room temperatureover short periods of time, e.g. few hours to few days, to few months.In such cases, the subsequent melt-annealing may be omitted if theincreased crystallinity and modulus resulting from the irradiation ispreferred. Otherwise, the subsequent melt-annealing may be carried outto decrease the crystallinity and modulus. In the case where meltannealing is omitted, the irradiated preform can be directly machinedinto the final medical device.

The reduction of residual free radicals to substantially undetectablelevels is particularly important if the polymer is used in themanufacture of any of the medical devices, such as orthopedic devices.

The reduction of free radicals to point where there are substantially nodetectable free radicals can be achieved by heating the polymer to abovethe melting point. The heating provides the molecules with sufficientmobility so as to eliminate the constraints derived from the crystals ofthe polymer, thereby allowing essentially all of the residual freeradicals to recombine. Preferably, the polymer is heated to atemperature between the peak melting temperature (PMT) and degradationtemperature (T_(d)) of the polymer, more preferably between about 3° C.above PMT and T_(d), more preferably between about 10° C. above PMT and50° C. above PMT, more preferably between about 10° C. and 12° C. abovePMT and most preferably about 15° C. above PMT.

Preferably, for UHMWPE the polymer is heated to a temperature of about137° C. to about 300° C., more preferably about 140° C. to about 300°C., more preferably yet about 140° C. to about 190° C., more preferablyyet about 145° C. to about 300° C., more preferably yet about 145° C. toabout 190° C., more preferably yet about 146° C. to about 190° C., andmost preferably about 150° C. Preferably, the temperature in the heatingstep is maintained for about 0.5 minutes to about 24 hours, morepreferably about 1 hour to about 3 hours, and most preferably about 2hours. The heating can be carried out, e.g., in air, in an inert gas,e.g., nitrogen, argon or helium, in a sensitizing atmosphere, e.g.,acetylene, or in a vacuum. It is preferred that for the longer heatingtimes, that the heating be carried out in an inert gas or under vacuumto avoid in-depth oxidation.

In certain embodiments, there may be a tolerable level of residual freeradicals in which case, the post-irradiation annealing can also becarried out below the melting point of the polymer.

b. Different Properties of Polymers Irradiated with Different Techniques

The various irradiation techniques described above may be used, eitherindividually or in combination, to yield a polymer with certain desiredproperties.

In the case of polyethylene, a semi-crystalline polymer with around 50%crystallinity, the irradiation method selected will significantlycontribute to the properties of the irradiated polymer. Whenpolyethylene is irradiated, even though the radiolytic reactions takeplace throughout the structure, the crosslinks form principally in theamorphous phase where there is limited hindrance to molecular mobility.See McGinniss, V., Crosslinking with radiation, in Polymer Handbook, J.Brandrup and E. H. Immergut, Eds. (1989); Dole, M., “Crosslinking andcrystallinity in irradiated polyethylene,” Polym.-Plast. Technol. Eng.,13(1): 41–46 (1979). Therefore, the IMS process leads to the uniformcrosslinking of all molecular chains by eliminating the crystals throughmelting, while the CI-SM process leads to a non-uniform crosslinkingonly in 50% of the chains. In the WIAM process, the polyethylene isheated to below its melting point to a crystallinity level of 40% andirradiated at a high dose rate. During irradiation, due to the heatgenerated by the irradiation, which follows a thermodynamic equilibrium,generated by the high dose rate more crystals are melted and madeavailable for crosslinking. Certain chains are present for the completeirradiation and receive the full dose level, while others only receive afraction of the dose left from the time they are melted. Consequently,the crosslink density distribution of the WIAM is highly non-statisticalcompared to the CI-SM and IMS (see FIG. 2 for a schematic description).In fact, the WIAM-treated polyethylene always exhibits at least twomelting peaks indicative of at least a two-phase structure. WIAM treatedPE that has a final temperature following irradiation that is lower thanthe melting temperature of the polymer will exhibit three melting peaks.If such polymer is subjected to subsequent melting, the three peaks willresolve into two. WIAM treated PE that has a final temperature followingirradiation that is at or above the melting temperature of the polymerwill exhibit two melting peaks. In contrast, there is only one meltingpeak with CISM and IMS treated PE. As a result, some material propertiesof the IMS, CISM, and WIAM crosslinked polyethylenes differsignificantly. Table I shows some of these expected changes in UHMWPE.

TABLE I IMS CISM WIAM Low High Low High Low High dose dose dose dosedose dose Modulus ↓ ↓ ↓ → ↓ → Yield Stress ↓ ↓ ↓ → ↓ → Yield Strain ↓ →↓ → ↓ → Ultimate Stress ↓ ↓ ↓ → ↓ → Ultimate Strain ↓ ↓ ↓ → ↓ → CreepResistance ↓ ↓ ↓ → ↓ ↑ Viscoelasticity□ ↓ ↓ ↓ ↓ → → Toughness ↓ ↓ ↓ ↓ →→ ↓: Decrease →: Little decrease or significiantly no change ↑: IncreaseLow dose ~2–3 Mrad High dose >>4 Mrad

The WIAM technique is not expected to alter the viscoelasticity of thepolymer even at high dose levels, which is a significant drawback of theother techniques as shown in Table I.

c. Sequence of Irradiation

In embodiments in which more than one method of irradiation is utilized,the sequence of the irradiation methods may be set to achieve aparticular result. In certain embodiments, the WIAM treatment of thepolymer may lead to bubbles and cracks due to low bulk strength of thepolymer (for instance some of the lower molecular weight polyethylenes).Therefore, one can use the CIR (with or without subsequent melting) at alow dose level (5–10 Mrad) to increase the bulk strength of the polymer,then subsequently use the WIAM process to achieve the desiredproperties. Other sequences will become apparent to the skilled personin view of the teachings contained herein.

3. Preferential Irradiation Shielding

The selective, controlled manipulation of polymers using radiationchemistry can, in another aspect, be achieved by preferentialirradiation shielding. By using a shield or shields made of selectedmaterials, selected thicknesses, selected geometry's, selected areas andutilization of the shields in a selected order, the overall propertiesof the irradiated polymer may be controlled and tailored to achieve adesired result, particularly in view of alterations that can be made inthe type of irradiation, the irradiation dose, dose rate and exposuretime and temperature, as well as the methodology used (for example, IMS,WIR, CIR, CIR-SM and WIAM).

a. Shield Material

The irradiation shield may be made from any material that will at leastshield in part polymer from the irradiation. Exemplary materials includeceramics, metals, and glass. Suitable ceramics include alumina andzirconia. Suitable metals include aluminum, lead, iron, and steel.Polymers also may be used as shields.

b. Shield Geometry's and Order

An irradiation shield may be provided in any shape, cross-section, orthickness.

It is well known in the art that the thickness of the shield willcontribute to the ability of the material to shield the irradiation.Accordingly, the thickness of the shield can be selected depending uponthe extent of shielding that is desired in the shielded portion. In thismanner, the depth of irradiation penetration can be controlled, or atotal shielding of irradiation of the covered areas can be achieved. Theiso-dose penetration (defined as the depth at which the dose equals thatat the e-beam incidence surface) and the dose-depth penetration profiledepend on the energy of the electrons used. See Section 6a.

Thus, effect of irradiation and shielding can be controlled through thematerials used in the shield, the thickness of the shield (constant orvariable), the extent to which the shield covers the area of thematerial being irradiated (full or partial), the order of shielding andirradiation, the type and extent of irradiation, and polymer selection.

c. Complete Coverage Shielding

UHMWPE (GUR 1050) was covered by aluminum shield of varying thicknesses(1, 3, 5, 7, 9, 11, 13, 15 mm) and irradiated either at room temperatureor at 125° C. The irradiation was carried out at E-Beam Services(Cranbury, N.J.) using the 10/50 Impela linear electron acceleratoroperated at 10 MeV and 50 kW. To determine the penetration profile ofthe effects of e-beam, spatial variation in the trans-vinylene contentin the irradiated UHMWPE specimens was determined. The GUR 1050 UHMWPEhas no detectable trans-vinylene unsaturations. The ionizing radiation,e-beam in the present case, leads to the formation of trans-vinyleneunsaturations, the content of which varies linearly with absorbedradiation dose.

FIG. 3 shows a schematic of the shield UHMWPE construct. Followingirradiation, the irradiated UHMWPE construct was machined in half andmicrotomed as shown in FIG. 4. The microtomed thin section was thenanalyzed using a BioRad UMA 500 infra-red microscope with an aperturesize of 100 μm by 50 μm as a function of depth away from theshield/UHMWPE interface at 1 mm increments. Each individual infra-redspectra was then analyzed by normalizing the area under thetrans-vinylene vibration at 965 cm⁻¹ to the that under the 1900 cm⁻¹after subtracting the respective baselines. The value obtained, that isthe trans-vinylene index (TVI), is directly proportional to the absorbedradiation dose level.

The following equation was used:

$\begin{matrix}{{TVI} = \frac{{\int_{950}^{980}{{A(w)}\ {\mathbb{d}w}}} - B_{1}}{{\int_{1850}^{1985}{{A(w)}\ {\mathbb{d}w}}} - B_{2}}} \\{B_{1} = \frac{\lbrack {{A(980)} + {A(950)}} \rbrack( {980 - 950} )}{2}} \\{B_{2} = \frac{\lbrack {{A(1850)} + {A(1985)}} \rbrack( {1985 - 1880} )}{2}}\end{matrix}$where A(w) is the infra-red absorbance measured at wave number, w, B₁ isthe area under the baseline of the trans-vinylene vibration and B₂ isthat of the baseline under the reference (1900 cm⁻¹) vibration.

FIG. 5 shows the variation of TVI in room temperature irradiated UHMWPEas a function of distance away from the shield/UHMWPE interface fordifferent shield thicknesses. FIG. 6 shows the same for the UHMWPE thatwas irradiated at 125° C. The figures clearly show that the penetrationof the effects of e-beam can be controlled by placing an aluminum shieldand by varying its thickness. The temperature at which the irradiationis being carried can also be used to change the profile of the beampenetration. This is illustrated in FIG. 7 where the variation in TVIwith depth is presented for three different shield thicknesses (1, 9,and 15 mm) and two irradiation temperatures (25° C. and 125° C.).

d. Paitial Coverage Shielding

UHMWPE (GUR 1050) was covered by a 1 cm thick aluminum shield with around opening in the center, as shown in FIG. 8. The UHMWPE/shieldconstruct was then irradiated at 150° C. using the Van de Graafgenerator at the High Voltage Research Laboratories of MassachusettsInstitute of Technology (Cambridge, Mass.). This partial shieldingscheme should lead to the irradiation of the central part of the UHMWPEcylinder. To confirm this, the spatial distribution of the effects ofe-beam was determined by measuring the content of trans-vinyleneunsaturations as a function of distance away from the side-wall to thecenter of the UHMWPE disc in the direction perpendicular to the e-beamincidence direction.

The GUR 1050 UHMWPE has no detectable trans-vinylene unsaturations. Theionizing radiation, e-beam in the present case, leads to the formationof trans-vinylene unsaturations, the content of which varies linearlywith absorbed radiation dose.

Following irradiation, the irradiated UHMWPE cylinder was machined inhalf and microtomed as shown in FIG. 9. The microtomed thin section wasthen analyzed using a BioRad UMA 500 infra-red microscope with anaperture size of 100 μm by 50 μm as a function of depth away from thesidewall to the center of the irradiated UHMWPE disk at 1 mm increments.Each individual infra-red spectra was then analyzed by normalizing thearea under the trans-vinylene vibration at 965 cm⁻¹ to the that underthe 1900 cm⁻¹ after subtracting the respective baselines. The valueobtained, that is the trans-vinylene index (TVI), is directlyproportional to the absorbed radiation dose level.

The following equation was used:

$\begin{matrix}{{TVI} = \frac{{\int_{950}^{980}{{A(w)}\ {\mathbb{d}w}}} - B_{1}}{{\int_{1850}^{1985}{{A(w)}\ {\mathbb{d}w}}} - B_{2}}} \\{B_{1} = \frac{\lbrack {{A(980)} + {A(950)}} \rbrack( {980 - 950} )}{2}} \\{B_{2} = \frac{\lbrack {{A(1850)} + {A(1985)}} \rbrack( {1985 - 1880} )}{2}}\end{matrix}$where A(w) is the infra-red absorbance measured at wave number, w, B₁ isthe area under the baseline of the trans-vinylene vibration and B₂ isthat of the baseline under the reference (1900 cm⁻¹) vibration.

FIG. 10 shows the variation of TVI in the irradiated UHMWPE as afunction of distance away from the sidewall of the shielded andirradiated UHMWPE. Under the shielded region, the TVI level was nearzero; while the value under the unshielded region increased, indicatingthe presence of radiation in this region.

The effect of irradiation with a disc shaped shield on UHMWPE also isillustrated in FIG. 11 where an unirradiated UHMWPE (panel a) andshield-irradiated UHMWPE (panel b) are shown. When the irradiation iscarried out above the melting point of UHMWPE, which is the case here,the crystallinity decreases significantly and melt-irradiated UHMWPEbecomes more transparent. This transparency is apparent in Figure panelb, in the region where the shield was not covering the UHMWPE disc. Thedecrease in the crystallinity is also associated with a decrease inmodulus. Therefore, one can use the procedure described here tomanufacture different shaped UHMWPE with regions of lower modulus forspecific medical applications.

The shape and cross-section of the shield also plays an important rolein determining the properties of the irradiated polymer. Any shape andcross-section shield, or combination of shapes and cross-sections, maybe utilized to achieve a desired cross-link depth and pattern.

FIG. 18 illustrates some exemplary shield edge geometry's and thehypothesized irradiation penetration envelopes resulting therefrom areshown in FIG. 20. In particular, depiction (A) FIG. 18 show arectangular cross-section. The cross-link pattern, when there is a fullblocking of irradiation, leaves most of the area under the shielduncross-linked. However, there is a portion of the polymer under eachedge of the shield that is cross-linked due to the electron penetrationenvelope. This pattern is the result of the “teardrop” signature left byelectron radiation as it travels through the polymer. This signature isdepicted in FIG. 20. FIG. 19 illustrates the effect of an irradiationshield on the depth of penetration of electron radiation at 10 MeV.

Depictions (B), (C), (G) and (H) illustrate an inclined or declinedcross-section and the resultant cross-linking pattern. Depictions (D)and (E) illustrate a curved cross-section and the resultantcross-linking pattern. Other cross-sections are attainable according tothe teachings contained herein.

Illustrative examples of suitable shield geometry's, cross-sections, andthe use of shielding in sequence are shown in FIGS. 12–17 and 21. FIG.21, for example, illustrates the irradiation of a polymer preform usingboth a ring-shaped and disc-shaped shield in sequence. Using acombination of ring and discs shields is an exemplary method of usingshielding to impart different properties to the core and periphery of apolymer preform.

e. Complete Coverage vs. Partial Coverage Shielding

“Complete” coverage shielding, denoting the use of a shield that coversthe entire surface of the polymer being irradiated, is characterized bya cross-linking gradient parallel to the direction of irradiation. Thatis, due to the shield (including, for example, a portion of the polymeritself), there will be differences in the degree of cross-linking,resulting in a gradient ranging from extensively cross-linked tonon-cross-linked, in the plane of the preform that is parallel to thevector that defines the direction of the radiation from the source tothe preform. Examples of complete coverage shielding are shown in FIGS.19, 23 and 24. In FIG. 23, the surface of the polymer is designed to beof sufficient thickness to act as a shield for the irradiation from theinner portion of the polymer. In other embodiments, other shields may beplaced on or over the surface of the polymer such that the depth ofpenetration of irradiation, as the resulting cross-linking, is affected.FIG. 24 shows a particular embodiment of complete coverage shielding inwhich the preform is rotated along an axis passing through the interiorof the preform. As FIG. 24 shows, this embodiment results in a gradientof cross-linking parallel to the vector that defines the direction ofthe radiation from the source to the preform and in which outer portionof the preform are more extensively cross-linked relative to the innerportion.

“Partial” coverage shielding, denoting the use of a shield that does notcover the entire surface of the polymer being irradiated, ischaracterized by a cross-linking gradient perpendicular to direction ofirradiation. That is, due to the shield, there will be differences inthe degree of cross-linking, ranging from extensively cross-linked tonon-cross-linked, in the plane of the preform that is perpendicular tothe vector that defines the direction of the radiation from the sourceto the preform. FIG. 22. Due to propagation of the electrons in theirradiated preform, a degree of cross-linking will occur under the outeredges of the shield, which are schematically depicted as tear drops inFIG. 20. Thus, where differential shielding has been performed, agradient of fuller cross-linking to comparatively lesser cross-linkingor no crosslinking will be observed in the plane represented by thedirectional arrow in (see FIG. 22). Thus, cross-linking will be greatestin the unshielded areas, begin to decrease at the interface of theshield and an unshielded (or lesser shielded) edge, and decreasefurther, or be absent altogether (depending upon the thickness andconsistency of the shield), at the inner portions under the shieldedarea.

4. Characterization Methodologies for Irradiated Polymers

a. Thermal Properties (Differential Scanning Calorimetry—DSC)

The thermal properties of the polymers are studied using a Perkin EhnerDSC-7 at a heating and cooling rate of 10° C./min to determine theparameters needed in the thermodynamic analysis of the WIAM process foreach polymer or polymer alloy. The heats of fusion, specific heats,crystallization, peak melting temperatures and crystallizationtemperatures are determined from the first heating and coolingendotherms. The cooling profile will be monitored to determine thevariations in the crystallization behavior of the test samples.

b. Other Methodologies

Cross-link densities, infra-red analyses and other analytical techniquesalso can be performed on irradiated samples using approaches known inthe art.

The invention is described in more detail in the following illustrativeexamples. Although the examples may represent only selected embodimentsof the invention, it should be understood that the following examplesare illustrative and not limiting.

5. Exemplary Uses for Orthopedic Applications and Other Examples

a. Acetabular Liner

This example describes a preferred embodiment of the selective,controlled manipulation of properties of polymers through radiationchemistry for the fabrication of an acetabular liner. In thisembodiment, the acetabular liner is crosslinked where the articulationtakes place. In the region of the locking mechanisms, the describedacetabular liner is not crosslinked in order to maintain the propertiesof the raw polymer. The irradiation procedure is schematically describedin FIG. 13. A preform polymer disc is shielded in the periphery duringthe irradiation process in order to avoid any crosslinking in the regionwhere the locking mechanism of the liner is machined. As shown in thisfigure, the shield is placed around the periphery. Crosslinking thenonly takes place in the central region where the articulating surface ofthe acetabular liner will reside when the final shape is machined fromthe preform. The shield is circular and the dimensions of it isdetermined based on the size of the acetabular liner that will bemachined. As shown in the figure, the shield is either a flat circulardisc or a circular disc with an incline to generate a smooth transitionof properties from crosslinked to uncrosslinked region. Subsequent toirradiation and prior to machining, the disc is heat treated to reducethe concentration of the residual free radicals to substantiallyundetectable levels as measured by electron spin resonance. The finalcomponent is machined carefully from the irradiated and annealed preformin order to make sure that the locking mechanisms are machined in theshielded region where there is no or little crosslinking and also thearticulating surface is machined from the region where there iscrosslinking achieved through the irradiation step of this example.

b. Mobile Bearing Knee I

In a mobile bearing knee (mbk), the tibial insert is free to move on thetibial base plate in different directions depending on the design.Because of this motion, the tibial insert will be in contact with stopsthat are machined onto the tibial plate. In order to minimize any longterm cyclic deformation of the polymer insert in regions where contactwith the stops occur, only the regions where the articulation will takeplace will be cross-linked. The contact regions will remainsubstantially uncross-linked. An example is schematically shown in FIG.14. The shield(s) is placed on top of the preform from which the tibialinsert will be machined. The location of the shield(s) is determinedbased on where the tibial insert will be engaging with the tibial baseplate during motion. The dimensions of the shield are based on thedesign and the size of the tibial insert that will be machined from thepreform. The shielded preform is irradiated with a preferred irradiationtechnique, the shield(s) is removed, and the preform is annealed aboveits melting point to reduce the concentration of the residual freeradicals to substantially undetectable levels as measured by electronspin resonance. Finally, the preform is machined into the tibial insertwhile ensuring that uncrosslinked parts are maintained within regionswhere contact with stops will take place.

It is also possible to selectively manipulate the properties of thepolymer used in the manufacturing of the mobile bearing tibial insert inregions where the insert will be in contact with the stops on the tibialbase plate by the use of shielded radiation chemistry. This is achievedby adding a second irradiation step following the first one described inthe above example. In this step, the preform is now shielded in regionswhere articulation will occur and only the regions where the tibialinsert will eventually be in contact with the stops are subjected toirradiation. The preferred method of irradiation will then be used toirradiate the shielded preform construct in order to achieve the desiredproperties in the regions where the insert will be in contact with thestops. The desired properties could be a reduction in elastic modulus,which can be achieved through irradiation in the molten state.

c. Mobile Bearing Knee II

In another embodiment, also shown in FIG. 14, it is also possible toselectively manipulate the properties of the polymer use in themanufacturing of the mobile bearing tibial insert in regions where theinsert will be rotating about a post on the tibial plate. This isachieved by shielded radiation chemistry. Similar to the embodimentdescribed above, the polymer preform is irradiated with a shield placedon the preform to block the electrons from where the tibial insert willbe rotating about the post. This ensures the crosslinking of thearticulating surfaces and does not compromise the properties of theinsert in the rotating region. Following the radiation, the shield isremoved and the preform is annealed above its melting point to reducethe concentration of residual free radicals to substantiallyundetectable levels with electron spin resonance. In another embodiment,the properties of the region where the rotation of the tibial insertwill occur can also be selectively controlled using shielded radiationchemistry. This is achieved by adding a second radiation step followingthe first one described in the above embodiment. The second stepinvolves the irradiation of the preform with a shield covering only thearticulating regions and not the region where the rotation will takeplace. The construct is then irradiated using the preferred radiationmethod, the shield is removed, the preform is annealed above its meltingpoint to reduce the concentration of residual free radicals tosubstantially undetectable levels, and the component is machined. Duringthe machining process, special care is taken to ensure that the rotatingregion of the tibial knee insert is machined from underneath the firstshield.

d. Knee Meniscus

An artificial knee meniscus can be manufactured into the tibial insertused in total knee replacements. This is achieved by the shieldedirradiation of a preform that will be used in the machining of the finaltibial insert. The artificial meniscus is located around the peripheryof the final component. The artificial meniscus should desirably havelower elastic modulus than the rest of the component. As shown in FIG.15, a shield is placed on top of the preform in order to avoid anyirradiation in the central region of the tibial plateau. This constructis then irradiated using the preferred electron beam irradiation methodto achieve the desired level of elastic modulus. The first shield isthen removed and replaced by another shield that covers the previouslyirradiated region. The shielded preform construct is then irradiated tocrosslink the central region using the desired irradiation method toachieve the desired level of wear resistance.

e. Shoulder Meniscus

In total shoulder replacements, the major problem is the fixation of theglenoid the failure of which is initiated by the rocking motion inducedby the humoral head. In order to reduce the rocking induced stresses atthe glenoid-cement or glenoid-bone interface, a shoulder glenoid with alower elastic modulus meniscus surrounding the periphery of the glenoidis manufactured. This is achieved similarly to the method described inthe knee meniscus example. As depicted in FIG. 16, a shield is placed inthe central region of the preform from which the glenoid will bemachined. The shielded preform construct is then irradiated with thepreferred method of irradiation that will lead to the desired level ofreduction of the elastic modulus. This is followed by the shielding ofthe periphery and irradiation of the central region using a desiredirradiation technique. The resulting product is then annealed in orderto reduce the concentration of the residual free radicals tosubstantially undetectable levels as measured by electron spinresonance. Then the glenoid component is machined from the preform whileensuring that the regions selectively irradiated to achieve lowerelastic modulus coincide with the synthetic meniscus or the periphery ofthe glenoid. In another embodiment, the reduced elastic modulus islimited to the superior and inferior regions of the glenoid where therocking motion is most prominent. This is again achieved by theselective controlled manipulation of the properties through shieldedirradiation methods.

f. Finger

A spacer for a finger joint is designed to avoid bone-on-bone contactand bone-on-bone articulation. In order to accomplish this, a spacerusing selective controlled manipulation of properties through radiationchemistry is manufactured. The proposed spacer is more compliant inregions where bending will occur to allow the motion of the finger. Inthe remaining regions, the spacer is less compliant and preferably wearresistant to prevent the generation of wear debris upon rubbing againstbone or any surface that may be present. FIG. 17 schematically shows theirradiation process. The preform from which the final spacer device willbe machined is irradiated with a shield in order to irradiate only thecentral region where the spacer will be bending during use. Theirradiation method is selected to achieve a reduced elastic modulus(increased compliance), decreased stresses, and increased fatigue lifeof the material in that region. The first shielded irradiation is thenfollowed by another irradiation step in which the central region isshielded and only the two extremes of the spacer areas are irradiatedusing the desired irradiation method. Following the two steps ofshielded irradiation, the preform is annealed in order to reduced theconcentration of the residual free radicals to substantiallyundetectable levels as measured by electron spin resonance. Themachining of the spacer is then carried out carefully to ensure that theregion where the elastic modulus is lower is maintained at the centralregion where the bending of the spacer will take place during use.

g. High Flex Knee

One of the major limitations of total knee replacements is the reducedrange of motion of the knee following the operation. An increased rangeof motion, that is increased flexion of the knee, is desirableespecially for cultures where deep knee bends are part of dailyactivities. For instance, in Islamic cultures, high flexion of the kneeis required for praying. In a total knee replacement in order to achievedeeper flexion angles, the femoral component would have to furthertranslate posteriorly. This, in most designs, will lead to the edgeloading of the posterior condyles of the tibial insert with the femoralcomponent. The result of this type of loading will be very high contactstresses and the potential premature failure of the edge of the tibialcondyles. The likelihood of snap mechanism failure and location of thetibial insert from the metal base plate will also increase. To avoidthese types of failures, improved total knee designs with increasedflexion angle will be needed.

To further reduce the risk of failure in either the existing or newdesigns, one can selectively manipulate the properties of thepolyethylene at the posterior edges of the condyles to reduce thecontact stresses. This can be done through selective controlledmanipulation of the properties of the polyethylene used in themanufacture of the tibial insert. For instance, the tibial knee insertcan be made up of warm irradiated, adiabatically melted (WIAM at 95 kGyof radiation dose and 125° C. of pre-irradiation temperature) UHMWPEwith the posterior condyles treated further with melt irradiation (IMSat 100 kGy at irradiation temperature of 140° C.). The further treatmentwith the IMS process will reduce the modulus of the already WIAM-treatedpolymer, hence reducing the contact stresses. This will also lead toreduced load transfer to the snap and locking mechanisms, hencepreventing snap/locking mechanism failures.

A similar result could be achieved by machining the tibial knee insertfrom a piece of UHMWPE that had been partially treated with a 125° C.,95 kGy WIAM process and partially treated with a 140° C., 100 kGy IMSprocess. The tibial knee insert is machined so that the posterior edgesof the condyles coincide with the part of the UHMWPE where IMS had beenapplied and the rest coincides with where the WIAM treatment had beenapplied.

6. Irradiation Parameters and Controlled Manipulation of IrradiatedPolymer Properties

a. Iso-Dose Penetration

The irradiation of materials with electrons leads to the well knownbuilt-up of absorbed dose level as a function of distance away from theelectron beam incidence surface. This built-up of the absorbed dose isdue to the generation of secondary electrons following the collision ofthe incident electrons with the atoms of the host material. Thecollisions generate more electrons at the expense of loosing kineticenergy while increasing the effective absorbed dose level as theelectron flux travels into the material. At a critical depth, thekinetic energy loss reaches a level where the electron flux slows downand leads to an abrupt decay in the absorbed dose level. The depth atwhich the absorbed dose level is equal to that at the surface is calledthe iso-dose penetration depth. This penetration increases with theincreasing energy of the incident electrons. Provided herein are twomethods of determining the iso-dose penetration of 10 MeV electrons intoUHMWPE, namely dosimetry and determination of trans-vinlyeneunsaturations.

For the dosimetry, irradiation was performed on a stack of 16 thinsections (3 mm) of UHMWPE (GUR 1050) sandwiched with three Far WestTechnology (Goleta, Calif.) dosimeters between each section as shown inFIG. 25. The dosimeters were then used to calculate an average doselevel as a function of e-beam penetration depth. Additionally, a 96 mmthick disc was irradiated, which was used for the trans-vinylene methodof quantifying the beam penetration. The e-beam irradiation was carriedout using a 10 MeV accelerator, Impela 10/50 (E-Beam Services, NJ, USA)operated at 40 kW power.

The 96 mm thick disc was microtomed (200 μm section) in the direction ofthe e-beam penetration. IR-spectra from this thin section were collectedusing a BioRad UMA 500 infra-red microscope. The spectra were collectedas a function of distance away from the e-beam incidence surface with astep size of 1 mm. IR spectra were collected on lightly polishedmicrotomed sections using a BioRad UMA500 IR-microscope with an aperturesize of 100 μm by 50 μm as a function of depth away from the e-beamincidence surface at 1 mm increments. The trans-vinylene index (TVI) wascalculated by normalizing the area under the trans-vinylene vibration at965 cm⁻¹ to that under the 1900 cm⁻¹ vibration after subtracting therespective baselines. The following equation was used:

$\begin{matrix}{{TVI} = \frac{{\int_{950}^{980}{{A(w)}\ {\mathbb{d}w}}} - B_{1}}{{\int_{1850}^{1985}{{A(w)}\ {\mathbb{d}w}}} - B_{2}}} \\{B_{1} = \frac{\lbrack {{A(980)} + {A(950)}} \rbrack( {980 - 950} )}{2}} \\{B_{2} = \frac{\lbrack {{A(1850)} + {A(1985)}} \rbrack( {1985 - 1880} )}{2}}\end{matrix}$where A(w) is the infra-red absorbance measured at wave number, w, B₁ isthe area under the baseline of the trans-vinylene vibration and B₂ isthat of the baseline under the reference (1900 cm⁻¹) vibration.

FIG. 26 shows the dosimeter measurement of the cascade effect and thatof the TVI method, where both the TVI values and the values obtainedfrom the dosimetry were normalized to their respective values measuredat the e-beam incidence surface. Both sets of data were in goodagreement, which shows strong evidence for the validity of the TVImethod in determining the dose variation as a result of the cascadeeffect. The build-up of the absorbed dose level is apparent with bothmethods and the approximate iso-dose penetration of the 10 MeV e-beamused is about 40 mm into UHMWPE.

b. Selective Controlled Reduction of the Elastic Modulus

The elastic modulus of the polymer can be reduced by using severaldifferent techniques. In one embodiment, the polymer is irradiated inits molten state in order to reduce the crystallinity and elasticmodulus of the polymer. In another embodiment, the polymer is irradiatedusing the WIAM technique and the elastic modulus is reduced byincreasing the irradiation dose levels. In another embodiment, thepolymer is irradiated using the CISM technique and the elastic modulusis reduced by using increased radiation dose levels. In a medical devicesuch as a finger joint spacer, shoulder meniscus, knee meniscus, ortibial knee inserts the regions where the elastic modulus is desirablylower can be achieved by using any one of the above techniques. In oneembodiment, the preform from which the device will be machined isshielded so that the electron beam penetration is limited to thoseregions that will selectively be treated to have lower elastic modulus.The preform is then irradiated with the desired irradiation method, suchas WIAM, irradiation in a molten state, or CISM. The shield is thenremoved and the preform is further irradiated with the desired methodwithout any more shielding. This leads to much higher cumulative doselevels in initially irradiated regions, where the low elastic modulus isdesired. The higher dose levels in these regions will then lead to lowerelastic modulus compared with the rest of the preform. In anotherembodiment, the preform from which the medical device will be machinedis irradiated with two steps of shielded irradiation. First, the regionswith the desired high elastic modulus are shielded against radiation andthe irradiation is carried out in order to reduce the elastic modulus ofthe regions that were exposed to the electron beam. The methods ofirradiation could be selected from any one of the methods describedabove. Then the shield is removed and replaced by another shield wherebythe regions with the now lower elastic modulus are covered to prevent orminimize further exposure. This shielded preform construct is thenirradiated with the preferred irradiation method to achieve the desiredproperties outside the regions with lower elastic modulus. Following thesecond irradiation step, the shield is removed and the preform isannealed in order to reduce the concentration of the residual freeradicals to undetectable levels as measured by electron spin resonance.Finally, the medical device is machined from the preform with care tomake sure that the lower elastic modulus regions coincide with parts ofthe medical device that are intended to have lower elastic modulus, forinstance, the meniscus in the tibial knee insert or the bending portionof the finger joint.

c. Residual Free Radicals

Depending on the polymer system used in the selective controlledmanipulation of properties in a preform to manufacture any of themedical devices described in the above embodiments, there may or may notbe detectable residual free radicals left in the material following theirradiation process. If there are residual free radicals remaining inthe material, these are reduced to substantially undetectable levels asmeasured by electron spin resonance through annealing of the preformsabove the melting point of the polymeric system used. The melt annealingallows the residual free radicals to re-combine with each other. If fora given system the preform substantially does not have any detectableresidual free radicals following irradiation, then the melt annealingstep is not utilized and the irradiated preform is directly machinedinto the final medical device.

The invention described herein may be embodied in other specific formswithout departing from the spirit or essential characteristics thereof.The specific embodiments previously described are therefore to beconsidered as illustrative of, and not limiting, the scope of theinvention. Additionally, the disclosure of all publications and patentapplications cited herein, including U.S. Pat. No. 5,879,400, U.S.Provisional Application Ser. No. 60/254,560, International ApplicationNo. PCT/US97/02220 (WO 97/29793), and International Application No.PCT/US99/16070, are expressly incorporated herein by reference in theirentireties to the same extent as if each were incorporated by referenceindividually.

1. An irradiated polymeric composition comprising polymers, wherein thepolymeric composition has a gradient of crosslink density in a directionperpendicular to the direction of irradiation, wherein a part of thepolymeric composition was preferentially shielded to partially blockradiation during irradiation in order to provide the gradient ofcrosslink density, wherein the preferential shielding is used where agradient of crosslink density is desired and the gradient of crosslinkdensity is in a direction perpendicular to the direction of irradiationon the preferentially shielded polymeric composition.
 2. The compositionof claim 1, wherein said polymer is selected from the group consistingof high density polyethylene, low density polyethylene, linear lowdensity polyethylene, ultra low density polyethylene, very low densitypolyethylene, ultra high molecular weight polyethylene, and highmolecular weight polyethylene.
 3. The composition comprising of claim 1,wherein the polymer is an alloy of two or more polymers selected fromthe group consisting of high density polyethylene, low densitypolyethylene, linear low density polyethylene, ultra low densitypolyethylene, very low density polyethylene, ultra high molecular weightpolyethylene, and high molecular weight polyethylene.
 4. The compositionof claim 1, wherein the polymer is ultra high molecular weightpolyethylene.
 5. A method of making a cross-linked polymeric compositioncomprising polymers, wherein the cross-linked polymeric composition hasa gradient of crosslink density in a direction perpendicular to thedirection of irradiation, said method comprising: (A) preferentiallyshielding to partially block radiation from a part of the composition;and (B) irradiating said preferentially shielded composition of (A) inorder to provide the gradient of crosslink density, wherein thepreferential shielding is used where a gradient of crosslink density isdesired and the gradient of crosslink density is in a directionperpendicular to the direction of irradiation of the preferentiallyshielded polymeric composition.
 6. The method of claim 5, wherein saidpolymer is selected from the group consisting of high densitypolyethylene, low density polyethylene, linear low density polyethylene,ultra low density polyethylene, very low density polyethylene, ultrahigh molecular weight polyethylene, and high molecular weightpolyethylene.
 7. The method of claim 6, wherein the polymer is ultrahigh molecular weight polyethylene.
 8. The method of claim 5, whereinirradiation step comprises one or more, in any order, of the proceduresselected from the group consisting of procedures (a)–(g): (a) (i)heating the polymer to at or above the melting temperature of thepolymer, and (ii) irradiating the polymer in the molten state; (b) (i)providing the polymer at or below room temperature, and (ii) irradiatingthe polymer; (c) (i) providing the polymer at or below room temperature,and (ii) irradiating the polymer with a high enough total dose and/or ata fast enough dose rate to generate enough heat in the polymer to resultin at least a partial melting bf the crystals of the polymer; (d) (i)providing the polymer at or below room temperature, (ii) irradiating thepolymer, and (iii) heating the irradiated polymer to at or above themelting temperature of the polymer; (e) (i) heating the polymer to atemperature above room temperature and below the melting temperature,and (ii) irradiating the heated polymer; (f) (i) heating the polymer toa temperature above room temperature and below the melting temperature,(ii) irradiating the heated polymer, and (iii) heating the irradiatedpolymer to at or above the melting temperature of the polymer; and (g)(i) heating the polymer to a temperature above room temperature andbelow the melting temperature, and (ii) irradiating the heated polymerwith a high enough total dose and/or at a fast enough dose rate togenerate enough heat in the polymer to result in at least a partialmelting of the crystals of the polymer.
 9. The method of claim 5,wherein said polymeric composition is shielded by a shield made from amaterial selected from the group consisting of ceramics, metals, glassesand polymers.
 10. A medical prosthesis comprising an irradiatedpolymeric composition comprising polymers, wherein the prosthesis has agradient of crosslink density in a direction perpendicular to thedirection of irradiation, wherein a part of the polymeric compositionwas preferentially shielded to partially block radiation duringirradiation in order to provide the gradient of crosslink density,wherein the preferential shielding is used where a gradient of crosslinkdensity is desired and the gradient of crosslink density is in adirection perpendicular to the direction of irradiation on thepreferentially shielded polymeric composition.
 11. The medicalprosthesis of claim 10, wherein said polymer is selected from the groupconsisting of high density polyethylene, low density polyethylene,linear low density polyethylene, ultra low density polyethylene, vey lowdensity polyethylene, ultra high molecular weight polyethylene, and highmolecular weight polyethylene.
 12. The medical prosthesis of claim 10,wherein the polymer is an alloy of two or more polymers selected fromthe group consisting of high density polyethylene, low densitypolyethylene, linear low density polyethylene, ultra low densitypolyethylene, very low density polyethylene, ultra high molecular weightpolyethylene, and high molecular weight polyethylene.
 13. The medicalprosthesis of claim 10, wherein the polymer is ultra high molecularweight polyethylene.
 14. A method of making a medical prosthesiscomprising an irradiated polymeric composition, wherein the medicalprosthesis has a gradient of crosslink density in a directionperpendicular to the direction of irradiation, said method comprising:(A) preferentially shielding to partially block radiation from a part ofthe composition; and (B) irradiating said preferentially shieldedcomposition of (A) in order to provide the gradient of crosslinkdensity, wherein the preferential shielding is used where a gradient ofcrosslink density is desired and the gradient of crosslink density is ina direction perpendicular to the direction of irradiation on thepreferentially shielded polymeric composition.
 15. The method of claim14, wherein said polymer is selected from the group consisting of highdensity polyethylene, low density polyethylene, linear low densitypolyethylene, ultra low density polyethylene, very low densitypolyethylene, ultra high molecular weight polyethylene, and highmolecular weight polyethylene.
 16. The method of claim 14, wherein thepolymer is ultra high molecular weight polyethylene.
 17. The method ofclaim 14, wherein irradiation step comprises one or more, in any order,of the procedures selected from the group consisting of procedures(a)–(g): (a) (i) heating the polymer to at or above the meltingtemperature of the polymer, and (ii) irradiating the polymer in themolten state; (b) (i) providing the polymer at or below roomtemperature, and (ii) irradiating the polymer; (c) (i) providing thepolymer at or below room temperature, and (ii) irradiating the polymerwith a high enough total dose and/or at a fast enough dose rate togenerate enough heat in the polymer to result in at least a partialmelting of the crystals of the polymer; (d) (i) providing the polymer ator below room temperature, (ii) irradiating the polymer, and (iii)heating the irradiated polymer to at or above the melting temperature ofthe polymer; (e) (i) heating the polymer to a temperature above roomtemperature and below the melting temperature, and (ii) irradiating theheated polymer; (f) (i) heating the polymer to a temperature above roomtemperature and below the melting temperature, (ii) irradiating theheated polymer, and (iii) heating the irradiated polymer to at or abovethe melting temperature of the polymer; and (g) (i) heating the polymerto a temperature above room temperature and below the meltingtemperature, and (ii) irradiating the heated polymer with a high enoughtotal dose and/or at a fast enough dose rate to generate enough heat inthe polymer to result in at least a partial melting of the crystals ofthe polymer.
 18. The method of claim 14, wherein said polymericcomposition is shielded by a shield made from a material selected fromthe group consisting of ceramics, metals, glasses and polymers.
 19. Anirradiated polymeric composition comprising polymers, wherein thepolymeric composition has a gradient of crosslink density in a directionperpendicular to the direction of irradiation, wherein the gradient ofcrosslink density is obtained by partial coverage shielding of thepolymeric composition to partially block radiation, wherein partialcoverage shielding is used where a gradient of crosslink density isdesired and the gradient of crosslink density is in a directionperpendicular to the direction of irradiation on the partial coverageshielding.
 20. A medical prosthesis comprising an irradiated polymericcomposition comprising polymers, wherein the prosthesis has a gradientof crosslink density in a direction perpendicular to the direction ofirradiation, wherein the gradient of crosslink density is obtained bypartial coverage shielding of the polymeric composition to partiallyblock radiation, wherein the partial coverage shielding is used where agradient of crosslink density is desired and the gradient of crosslinkdensity is in a direction perpendicular to the direction of irradiationon the partial coverage shielding.
 21. A method of making a cross-linkedpolymeric composition comprising polymers, wherein the cross-linkedpolymeric composition has a gradient of crosslink density in a directionperpendicular to the direction of irradiation, wherein the methodcomprising: (A) partial coverage shielding of the polymeric compositionto partially block radiation; and (B) Irradiating the partially shieldedcomposition of (A) in order to provide the gradient of crosslinkdensity, wherein the partial coverage shielding is used where a gradientof crosslink density is desired and the gradient of crosslink density isin a direction perpendicular to the direction of irradiation on thepartial coverage shielding.
 22. A method of making a medical prosthesiscomprising an irradiated polymeric composition comprising polymers,wherein the medical prosthesis has a gradient of crosslink density in adirection perpendicular to the direction of irradiation, said methodcomprising: (A) partial coverage shielding of the composition topartially block radiation; and (B) irradiating the partially shieldedcomposition of (A) in order to provide the gradient of crosslinkdensity, wherein the partial coverage shielding is used where a gradientof crosslink density is desired and the gradient of crosslink density isin a direction perpendicular to the direction of irradiation on thepartial coverage shielding.